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http://dx.doi.org/10.5483/BMBRep.2010.43.4.245

Inhibitory effects of KHG26377 on glutamate dehydrogenase activity in cultured islets  

Yang, Seung-Ju (Department of Biomedical Laboratory Science, Konyang University)
Hahn, Hoh-Gyu (Division of Life Sciences, Korea Institute of Science and Technology)
Choi, Soo-Young (Department of Biomedical Sciences and Research Institute for Bioscience and Biotechnology, Hallym University)
Cho, Sung-Woo (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine)
Publication Information
BMB Reports / v.43, no.4, 2010 , pp. 245-249 More about this Journal
Abstract
GDH has been known to be related with hyperinsulinism-hyperammonemia syndrome. We have screened new drugs with a view to developing effective drugs modulating GDH activity. In the present work, we investigated the effects of a new drug, KHG26377 on glutamate formation and GDH activity in cultured rat islets. When KHG26377 was added to the culture medium for 24 h prior to kinetic analysis, the $V_{max}$ of GDH was decreased by 59% whereas $K_m$ is not significantly changed. The concentration of glutamate decreased by 50% and perfusion of islets with KHG26377 reduced insulin release by up to 55%. Our results show that KHG26377 regulates insulin release by inhibiting GDH activity in primary cultured islets and support the previous studies for the connection between GDH activity and insulin release. Further studies are required to determine in vivo effects and pharmacokinetics of the drug.
Keywords
Glutamate dehydrogenase; Hyperinsulinism; Inhibitor; KHG26377;
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